Download Near-fatal outcome after administration of hyoscine-N-butylbromide (Buscopan )

Case Studies: Near-fatal outcome after administration of hyoscine-N-butylbromide (Buscopan®)
Near-fatal outcome after administration of
hyoscine-N-butylbromide (Buscopan®)
Milner A, MBBCh, FFA(SA), MPharmMed, FRCP(C), PGPCCE(Melb)
Department of Anaesthesia, University of Pretoria, Pretoria, South Africa
Correspondence to: Professor Analee Milner, e-mail address: [email protected]
Keywords: anaphylaxis; angioneurotic oedema; hyoscine-N-butylbromide; porphyria
Abstract
While undergoing conscious sedation for a gastroscopy, an 18-year-old female developed severe hypotension
and loss of consciousness. This occurred shortly after an intravenous dose of hyoscine-N-butylbromide
(Buscopan®). Resuscitation was performed over a period of 10 minutes and was successful. Once conscious,
the patient complained of severe lower abdominal pain. Except for a significant metabolic acidosis (BE = -10),
initial investigations were negative. She was transferred to the Intensive Care Unit (ICU) where the abdominal
pain continued and the urine output was scanty for the first 12 hours. Investigations were done to exclude:
anaphylaxis, mesenteric ischaemia, angioneurotic oedema, pregnancy, porphyria, autoimmune disease and
myocardial ischaemia. Finally it was postulated that the drug had either caused an anaphylactoid reaction
or grossly augmented cardiovagal nervous inhibition. This resulted in hypotension which caused mesenteric
ischaemia that in turn resulted in severe abdominal pain and a degree of renal shutdown.
S Afr J Anaesthesiol Analg 2010;16(4):38-41
Introduction
Quaternary ammonium anticholinergic agents usually
have some ganglion-blocking activity so that high
doses may cause postural hypotension, but in toxic
doses non-depolarising neuromuscular blockade and
complete respiratory and cardiovascular collapse may
be produced.1 Side effects may be increased with the
simultaneous administration of other anticholinergic
agents and other centrally acting drugs.
There have been many reports of adverse reactions
to hyoscine-N-butylbromide.1-5 This case is of
special interest due to the complicated differential
diagnosis. Hyoscine-N-butylbromide is frequently
used for gastrointestinal spasm. It is a quaternary
ammonium anticholinergic agent, acting primarily on
parasympathetic ganglia in the walls of the viscera.1
Here it exerts a specific antispasmodic action on
smooth muscle in the gastrointestinal, biliary and
urinary tracts.
Case report
An eighteen-year-old female presented for gastroscopy. She gave no history of allergies or previous
anaesthetic problems. She had received 20 mg
hyoscine-N-butylbromide (Buscopan®) IV for
abdominal cramps and Depo Provera IM for contraception two weeks prior to this procedure.
Being an anticholinergic agent, all side effects and
precautions cited for atropine should be applicable.
Patients with glaucoma, urinary or gastrointestinal
tract obstruction, unstable cardiovascular status and
reflux oesophagitis should not be given this drug. This
drug should be used with caution in patients with
impaired metabolic, kidney and liver abnormalities.
Her vital signs were normal; blood pressure was
100/60 mmHg and pulse 85 beats/minute. Apart
from appearing extremely anxious, nothing abnormal
was detected. Informed consent was obtained for
conscious sedation.
Futhermore, side effects such as dry mouth,
tachycardia, blurred vision, confusion and cognitive
impairment may be a problem. Hypersensitivity
reactions, particularly skin reactions, have been
described.
S Afr J Anaesthesiol Analg
Monitoring was instituted according to the
recommendations of the South African Medical
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Case Studies: Near-fatal outcome after administration of hyoscine-N-butylbromide (Buscopan®)
Association.6 A pulse oximeter and a non-invasive
blood pressure device (NIBP) were connected. Oxygen
was given via nasal cannulae. A 22G intravenous
cannula was inserted into the dorsum of her right hand
and an infusion of Lactated Ringers was initiated. The
sedation consisted of: sufentanil 10 μg, midazolam
2 mg and, when the gastroenterologist was about to
insert the gastroscope, 40 mg propofol was added.
The patient complained of severe cramp-like lower
abdominal and pelvic pain. She continued to receive
100% oxygen by mask. An additional infusion of
hetastarch was initiated. Gradually her vital signs
stablised as the blood pressure rose above 100 mmHg
systolic and the pulse dropped below 95 beats/minute.
While still on the operating table the following tests
were done:
1. A 12-lead ECG, that showed a sinus tachycardia,
but no ischaemia.
2. An arterial blood gas that showed a severe
metabolic acidosis with pH = 7.31, BE = -10 and
HCO3- = 18.
3. A cardiologist examined her heart and a
transthoracic echocardiograph was done while
the patient was still on the operating table. Her
heart appeared normal.
4. A radiologist did an ultrasound of her uterus and
ovaries, which also appeared normal.
Her blood pressure dropped to 85/55 mmHg and her
pulse rate slowly drifted down to 48/minute and then
44/minute. The oxygen saturation (SaO2) remained
at 100% throughout. The slowing of the pulse rate
did not cause concern as she was young, it was a
“sleeping pulse”, and she had received an opioid and
propofol.
Approximately four minutes after the start of the
gastroscopy, 20 mg of hyoscine-N-butylbromide
was given intravenously. At this point the pulse was
42/minute, the SaO2 saturation 100% and the blood
pressure 85/55 mmHg.
She was then transferred to the ICU and monitored
for the next 24 hours. She continued to complain
of severe lower abdominal pain. No bowel sounds
were present, but her abdomen was soft. A general
surgeon was consulted to rule out the possibility of
mesenteric ischaemia. When she began menstruating
a gynaecologist was consulted and the β-HCG to
rule out an aborting pregnancy was negative. Her
urine output was relatively scanty as she passed
approximately 400 ml over an eight hour period. She
also complained of chest pain and this was thought to
be due to the cardiac massage.
A tachycardia of 140 beats/min occurred almost
immediately. The gastroenterologist commented
that the gastric mucosa appeared mottled with
areas of extreme blanching, indicative of severe
vasoconstriction. The patient began to cough and
groan. A further 20 mg propofol was given, but did not
appear to sedate her. The heart rate went up to 150/
minute and the NIBP monitor was “unable to record”.
No peripheral pulses were present, but a weak central
pulse was palpable.
The gastroscope was removed, the patient turned
on to her back and an ECG monitor was immediately
connected. At this point she was still breathing
spontaneously, but the oximeter probe was no
longer registering. The operating table was placed in
Trendellenburg and the infusion of Lactated Ringer’s
was increased to facilitate a faster flow. Cardiac
massage was initiated and adrenaline was titrated
in 100 μg increments. The first recordable blood
pressure of 40 mmHg systolic was then measured
with a manual sphygmonometer.
Her arterial blood gases gradually normalised. Twentyfour hours post cardiac arrest, a significant diuresis
occurred. She passed 1 500 ml urine over a two hour
period. She was discharged from ICU later that day.
The following blood tests were done in an attempt
to determine the exact cause of the cardiovascular
collapse:
a. Anaphylaxis: serum tryptase specific IgE
antibodies3
b. Angioneurotic oedema: C1-INH
c. Pregnancy: β-HCG
d. Autoimmune disease: antinuclear factor
e. Myocardial ischaemia: cardiac enzymes.
At this point the respiration was erratic and manual
ventilation with 100% oxygen was intiated, followed by
tracheal intubation and mechanical ventilation. The next
blood pressure recorded by the NIBP was 60 mmHg
systolic. A further 500 μg of adrenaline was titrated over
60 seconds. Her blood pressure rose to 85/50 mmHg
and her pulse came down to 135/minute. She regained
consciousness and pulled out her endotracheal tube.
The time from administration of the drug to her extubation
was nine and a half minutes.
S Afr J Anaesthesiol Analg
Urine was also tested, for porphyrins and urinary methyl
histamine to exclude porphyria and anaphylaxis.
Discussion
Hyoscine-N-butyl bromide is known to cause adverse
cardiovascular side effects.2,3,4,7 Anaphylaxis and
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Case Studies: Near-fatal outcome after administration of hyoscine-N-butylbromide (Buscopan®)
angioneurotic oedema appear high on the list and
needed to be excluded. Although bronchocutaneous
manifestations need not be present for both these
conditions, the absence of urticaria and bronchospasm
should force the physician to include other pathologies
in the differential diagnosis.
d.
A haemorrhage caused by an ectopic pregancy
or incomplete abortion causing a haemodynamic
collapse
and
lower
abdominal
pain.
e.
An anaphylactoid reaction, causing a “shock”-like
picture.
Scopolamine has been known to markedly and
paradoxically augment cardiovagal nervous inhibition
in healthy young subjects.7 in this study low dose
scopolamine was postulated to decrease blood
pressure by increasing sympathetic cholinergic
outflow in the vessels of striated muscle.
f.
Angioneurotic oedema. This patient had
abdominal pain, but no other oedema was evident.
Hereditary angioneurotic oedema is an autosomal
dominant state associated with the absence of
functional C1-INH. The diagnosis suggested
not only by family history but also by the lack of
urticarial reactions and the predominant signs of
gastro-intestinal attacks of colic, and episodes of
laryngeal oedema.2
After the anti-muscurinic agent was administered,
severe vasoconstriction of the gastric mucosa
occurred, as seen by the intense blanching of
the gastric mucosa. As acetyl choline normally
causes vasodilatation,7 it is logical to assume that
an antimuscurinic must cause some degree of
vasoconstriction. In our patient the constriction must
have been so severe that a degree of mesenteric
ischaemia occurred and probably was the cause of
her arousal prior to the gastroscope removal.
Transthoracic echocardiography in this patient was
normal, she had no apparent anatomical abnormality
that would make her unable to tolerate a sinus
tachycardia of 150 beats/min.
Clinically she did not appear to be dehydrated and her
reaction to the anaesthetic agents used for conscious
sedation was not consistent with that of a dehydrated
patient.
Shortly after this the blood pressure then dropped
to such an extent that she lost consciousness and
renal shutdown resulted. A severe metabolic acidosis
reflected this acute peripheral and central shutdown.
An ultraound of her uterus and ovaries was negative;
a negative β-HCG ruled out a possible complicating
pregnancy.
At the time of the haemodynamic collapse, the cause
was not evident and the following aethiologies had to
be excluded:
a.
b.
c.
In a few cases angioneurotic oedema has been
reported as a side effect of this drug. Although this
patient had severe abdominal pain, she had none of
the other signs of this condition such as urticarial skin
lesions and laryngeal oedema.
Abnormal cardiac anatomy, such as a left
ventricular outflow tract obstruction (HOCAM) or
aortic stenosis. This would imply that the patient
would be unable to maintain a cardiac output as
the heart rate rose significantly after the antimuscurinic agent. It is known that young patients
react with a greater degree of tachycardia to
all antimuscurinic agents than older patients.6
By exclusion, an anaphylactiod reaction seems the
most probable cause. However, she had none of the
other clinical signs that usually accompany these
reactions, such as bronchospasm, urticaria and
weals. It is postulated that 25% of anaphylactoid/
anaphylactic reactions do not manifest these usual
bronchocutaneous signs. Unfortunately not all of
the blood tests to investigate anaphylaxis were done
such as serum tryptase, urinary methyl histamine and
specific IgE antibodies.3
Tachy-dysrhythmia caused a drop in cardiac
output. She did not have continuous ECG
monitoring at the time she received hyoscine.
According to the South African Medical
Association guidelines, a continuous ECG
monitor is only necessary during conscious
sedation if the patient has some cardiac
problem.5 The patient was a young healthy adult.
Conclusion
Immediately after the administration of hyoscine
N-butylbromide, this patient presented with
cardiovascular collapse that caused a loss of
consciousness that necessitated intubation and
the use of 1 500 μg of adrenaline. She developed a
metabolic acidosis, renal shutdown and probably
Hypovolaemia due to the enforced period of
starvation for eight hours prior to the gastroscope.
At the time of the cardiovascular collapse she
had received about 300 ml of Lactated Ringers.
S Afr J Anaesthesiol Analg
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Case Studies: Near-fatal outcome after administration of hyoscine-N-butylbromide (Buscopan®)
mesenteric ischaemia that persisted for eight
hours post-operatively.
3.
4.
Blood tests to confirm an anaphylactic reaction were
not done, but by exclusion the most likely cause was
an anaphylactoid reaction after the administration of
hyoscine N-butylbromide.
5.
6.
7.
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Laxemaire MC, et al. 14–18.
Treweeke P, Barrett NK. Allergic reaction to Buscopan. A
letter. BJRad. 1987;60:417–8.
Thomas AMK, Kubie AM, Britt RP. Angioneurotic oedema
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